Tilting Behavior of Lamellar Ice Tip during Unidirectional Freezing of Aqueous Solutions.
Freezing of ice has been largely reported from many aspects, especially its complex pattern formation. Ice grown from liquid phase is usually characteristic of lamellar morphology that plays a significant role in various domains. However, tilted growth of ice via transition from coplanar to noncoplanar in directional solidification has been paid little attention in previous studies and there was a misleading explanation of the formation of tilted lamellar ice. Here, we in situ investigated the variations of tilting behavior of lamellar ice tips under different conditions within a single ice crystal of manipulated orientation via unidirectional freezing of aqueous solutions. It is found that tilted growth of ice tips is sensitive to pulling velocity and solute type. These experimental results reveal intrinsic tilted growth behavior of lamellar ice, which is suggested to enrich our understanding of pattern formation of ice in relevant physical processes.


Gut microbiome differences among Mexican Americans with and without type 2 diabetes mellitus.
Type 2 diabetes mellitus (T2DM) is an urgent public health problem and disproportionately affects Mexican Americans. The gut microbiome contributes to the pathophysiology of diabetes; however, no studies have examined this association in Mexican-Americans. The objective of this study was to compare gut microbiome composition between Mexican-Americans with and without T2DM. This was a cross-sectional study of volunteers from San Antonio, TX. Subjects were 18 years or older and self-identified as Mexican American. Subjects were grouped by prior T2DM diagnosis. Eligible subjects attended a clinic visit to provide demographic and medical information. Thereafter, subjects recorded their dietary intake for three days and collected a stool sample on the fourth day. Stool 16s rRNA sequences were classified into operational taxonomic units (OTUs) via the mothur bayesian classifier and referenced to the Greengenes database. Shannon diversity and bacterial taxa relative abundance were compared between groups using the Wilcoxon rank sum test. Beta diversity was estimated using Bray-Curtis indices and compared between groups using PERMANOVA. Thirty-seven subjects were included, 14 (38%) with diabetes and 23 (62%) without diabetes. Groups were well-matched by body mass index and comorbid conditions. Shannon diversity was not significantly different between those with and without T2DM (3.26 vs. 3.31; p = 0.341). Beta diversity was not significantly associated with T2DM diagnosis (p = 0.201). The relative abundance of the most common bacterial phyla and families did not significantly differ between groups; however, 16 OTUs were significantly different between groups. Although alpha diversity was not significantly different between diabetic and non-diabetic Mexican Americans, the abundance of certain bacterial taxa were significantly different between groups.


Self-Learning Molecular Design for High Lithium-Ion Conductive Ionic Liquids using Maze Game.
A self-learning artificial intelligence system for an autonomous molecular search was recently utilized in place of laborious material development processes by humans. In this approach, because the evaluation of unsuitable or unrealistic candidates considerably decreases the search efficiency, prior knowledge of the chemistry and engineering requirements should be embedded into the molecular-generative algorithm. However, when using naive rule-based restrictions, one must implement the complex rule logic into the code each time, depending on the materials and potential applications. Herein, we propose a molecular-generative method using a maze game to control the allowable constituent fragments of molecules, which improves the flexibility and consistency to implement the rules. We performed an autonomous search for optimized cation structures of high Li-ion conductive ionic liquids evaluated by molecular dynamics simulations, in its practically reasonable scope defined by the maze game. From the search, we discover that acyl ammonium cations are favorable for high Li-ion conductivity because of the high association between the cations and Li ions. These results broaden our existing insight owing to the ability to explore beyond our practical experiences.


Identification of single gene deletions at 15q13.3: further evidence that CHRNA7 causes the 15q13.3 microdeletion syndrome phenotype.
The 15q13.3 microdeletion syndrome (OMIM #612001) is characterized by a wide range of phenotypic features, including intellectual disability, seizures, autism, and psychiatric conditions. This deletion is inherited in approximately 75% of cases and has been found in mildly affected and normal parents, consistent with variable expressivity and incomplete penetrance. The common deletion is approximately 2 Mb and contains several genes; however, the gene(s) responsible for the resulting clinical features have not been clearly defined. Recently, four probands were reported with small deletions including only the CHRNA7 gene. These patients showed a wide range of phenotypic features similar to those associated with the larger 15q13.3 microdeletion. To further correlate genotype and phenotype, we queried our database of >15,000 patients tested in the Mayo Clinic Cytogenetics Laboratory from 2008 to 2011 and identified 19 individuals (10 probands and 9 family members) with isolated heterozygous CHRNA7 gene deletions. All but two infants displayed multiple features consistent with 15q13.3 microdeletion syndrome. We also identified the first de novo deletion confined to CHRNA7 as well as the second known case with homozygous deletion of CHRNA7 only. These results provide further evidence implicating CHRNA7 as the gene responsible for the clinical findings associated with 15q13.3 microdeletion.


Transglutaminase 4 as a prostate autoantigen in male subfertility.
Autoimmune polyendocrine syndrome type 1 (APS1), a monogenic disorder caused by AIRE gene mutations, features multiple autoimmune disease components. Infertility is common in both males and females with APS1. Although female infertility can be explained by autoimmune ovarian failure, the mechanisms underlying male infertility have remained poorly understood. We performed a proteome-wide autoantibody screen in APS1 patient sera to assess the autoimmune response against the male reproductive organs. By screening human protein arrays with male and female patient sera and by selecting for gender-imbalanced autoantibody signals, we identified transglutaminase 4 (TGM4) as a male-specific autoantigen. Notably, TGM4 is a prostatic secretory molecule with critical role in male reproduction. TGM4 autoantibodies were detected in most of the adult male APS1 patients but were absent in all the young males. Consecutive serum samples further revealed that TGM4 autoantibodies first presented during pubertal age and subsequent to prostate maturation. We assessed the animal model for APS1, the Aire-deficient mouse, and found spontaneous development of TGM4 autoantibodies specifically in males. Aire-deficient mice failed to present TGM4 in the thymus, consistent with a defect in central tolerance for TGM4. In the mouse, we further link TGM4 immunity with a destructive prostatitis and compromised secretion of TGM4. Collectively, our findings in APS1 patients and Aire-deficient mice reveal prostate autoimmunity as a major manifestation of APS1 with potential role in male subfertility.


Transformation-sensitive protein with molecular weight of 45,000 secreted by mouse fibroblasts.
The [35S]methionine-labeled proteins released in the medium conditioned by normal and transformed mouse fibroblasts have been analyzed by sodium dodecyl sulfate-polyacrylamide electrophoresis. Three major proteins, fibronectin, procollagens, and a protein with a molecular weight of 45,000 (45K protein) have been identified. The 45K protein, which has not yet been described, accounts for about 30% of the proteins released by control 3T3 fibroblasts or mouse embryo cultures. Quantitation of the radioactivity incorporated by the 45K protein indicated a 10- to 15-fold decrease in 3T3 fibroblasts transformed by Kirsten, Abelson, or Rous sarcoma viruses. The amounts of fibronectin and procollagens released in the medium by transformed cells were also reduced by factors of 3- and 5-fold, respectively. Pulse chase experiments have shown that the decreased level of the 45K protein in the medium of transformed cells cannot be explained by a reduced rate of secretion or by extracellular proteolytic degradation. It is not known, however, whether decreased synthesis is responsible for this alteration. The "tumor promoter" phorbol myristate acetate, which is known to induce many of the alterations associated with neoplastic cells, also induced 3T3 fibroblasts to release the 45K protein in amounts comparable to that of transformed cells. Thus, this protein represents a new molecular marker of oncoviral transformation.


Sedimentary noise and sea levels linked to land-ocean water exchange and obliquity forcing.
In ancient hothouses lacking ice sheets, the origins of large, million-year (myr)-scale sea-level oscillations remain a mystery, challenging current models of sea-level change. To address this mystery, we develop a sedimentary noise model for sea-level changes that simultaneously estimates geologic time and sea level from astronomically forced marginal marine stratigraphy. The noise model involves two complementary approaches: dynamic noise after orbital tuning (DYNOT) and lag-1 autocorrelation coefficient (ρ1). Noise modeling of Lower Triassic marine slope stratigraphy in South China reveal evidence for global sea-level variations in the Early Triassic hothouse that are anti-phased with continental water storage variations in the Germanic Basin. This supports the hypothesis that long-period (1-2 myr) astronomically forced water mass exchange between land and ocean reservoirs is a missing link for reconciling geological records and models for sea-level change during non-glacial periods.


Pharmacokinetics of Intravenous and Oral Phenobarbital Sodium in Healthy Goats.
Phenobarbital is a common drug used to manage epilepsy in goats. However, the recommended dose and dosing frequency are based on studies in dogs and horses. Studies describing the pharmacokinetics of phenobarbital when administered orally and assessing changes in behavior with concurrent electroencephalogram (EEG) readings are warranted in goats. The objectives of this study were to determine the bioavailability of orally administered phenobarbital and determine the effect of phenobarbital on brain activity using EEG in healthy goats. A cross-over design with 8 non-pregnant goats was performed. The goats were administered phenobarbital intravenously at 10 mg/kg, followed by a 2 week wash out period, and then administered phenobarbital, orally, at 10 mg/kg. Plasma sample determination of phenobarbital concentrations were collected at 13 time points. Continuous EEG readings with simultaneous video recording for 12 h was performed to determine the state of vigilance using a behavior scoring system prior to and after phenobarbital administration. Bioavailability of phenobarbital was 24.9%. Mean ± SD for half-life was similar between the oral (3.80 ± 0.826 h) and intravenous (4.0 ± 0.619 h) routes. Time to observed maximum concentration (Tmax), and maximum plasma concentration (Cmax) for the oral administration were 1.75 ± 0.46 h and 4,478.7 ± 962.4 ng/mL, respectively. Clearance was 152.5 ± 102.7 ml/h/kg. Area under the curve from zero to infinity (AUC0→∞) was 155,813 ± 218,448 and 38,763 ± 9,832 h*ng/mL for the intravenous and oral administration routes, respectively. Behavior score at 3 h after phenobarbital administration was different (P = 0.0002) from the score prior to administration for the oral administration route. In contrast, behavior scores before administration of phenobarbital and each time point after administration were not different (P >0.05) for the intravenous administration route or other oral administration route time points. Bioavailability of phenobarbital was poor, and the half-life was very short due to a high clearance. Doses >10 mg/kg should be considered when phenobarbital is administered orally in goats.


Predictive value of bacterial analysis of laparotomy wounds.
Despite improvements in antibiotic prophylaxis, surgical site infections represent the most common postoperative complication with important clinical consequences for patients. The hypothesis that a bacterial analysis of the surgical wound in the operating room could predict the likelihood of developing a clinical infection, and might allow a tailored and preemptive approach, aimed to reduce the consequences of an infection, seems appealing. We would like to present a prospective study on the predictive value of the bacterial analysis of laparotomy wounds. Seventy eight prospective patients undergoing surgery were included in the study. To evaluate the risk factors associated with increased rate of wound infection, we performed a bacterial analysis of the wound. 48 patients out of 78 (61%) had positive cultures. 23 patients out of 32 patients (72%) who didn't receive antibiotic prophylaxis were positive to the wound culture whereas 25 patients out of 46 patients (54%) grew positive cultures in the group of patients that received antibiotic prophylaxis. None of the 30 patients with negative cultures developed clinical infection. Only 6 patients out of 48 patients who had positive cultures (12.5%) developed wound infection. Clinical infection occurred in 5 patients who had gram-negative contamination of the wound. No clinical infection occurred in patients who had gram-positive contamination. Wound cultures and their positivity are predictive tools to identify the patients that are at risk to develop wound infection. The positive predictive value of the bacterial analysis of the wound was 12.5%. Abdominal surgery, Bacterial analysis, Wound infection.


Annexin 1: differential expression in tumor and mast cells in human larynx cancer.
Annexin 1 protein (ANXA1) expression was evaluated in tumor and mast cells in human larynx cancer and control epithelium. The effect of the exogenous ANXA1 (peptide Ac 2-26) was also examined during the cellular growth of the Hep-2 human larynx epidermoid carcinoma cell line. This peptide inhibited the proliferation of the Hep-2 cells within 144 hr. In surgical tissue specimens from 20 patients with larynx cancer, ultrastructural immunocytochemistry analysis showed in vivo down-regulation of ANXA1 expression in the tumor and increased in mast cells and Hep-2 cells treated with peptide Ac2-26. Combined in vivo and in vitro analysis demonstrated that ANXA1 plays a regulatory role in laryngeal cancer cell growth. We believe that a better understanding of the regulatory mechanisms of ANXA1 in tumor and mast cells may lead to future biological targets for the therapeutic intervention of human larynx cancer.


Semiparametric smoothing of discrete failure time data.
An estimator of the hazard rate function from discrete failure time data is obtained by semiparametric smoothing of the (nonsmooth) maximum likelihood estimator, which is achieved by repeated multiplication of a Markov chain transition-type matrix. This matrix is constructed so as to have a given standard discrete parametric hazard rate model, termed the vehicle model, as its stationary hazard rate. As with the discrete density estimation case, the proposed estimator gives improved performance when the vehicle model is a good one and otherwise provides a nonparametric method comparable to the only purely nonparametric smoother discussed in the literature. The proposed semiparametric smoothing approach is then extended to hazard models with covariates and is illustrated by applications to simulated and real data sets.


Acute eosinophilic appendicitis and the significance of eosinophil - Edema lesion.
Eight cases of a histological entity that we name 'acute eosinophilic appendicitis' (AEA) are described and compared with classical acute appendicitis and appendices, which turned out to be normal after emergency appendicectomy. These 8 cases formed part of a dataset of 128 emergency appendicectomies, which also included 78 cases of classical acute appendicitis and 42 cases of normal appendix. The clinical and pathological variables were compared between these three. Acute eosinophilic appendicitis is characterized by acute presentation and a grossly inflamed appendix, but with absence of neutrophils in the muscle layer. The histological hallmark of the entity is eosinophil infiltration of the muscularis propria with accompanying edema separating muscle fibers (the Eosinophil - Edema lesion). The duration and prevalence of symptoms, the male female ratio and the gross maximum circumference of the appendix in these 8 cases resembled classical acute appendicitis rather than those cases in which the morphology of the appendix was normal. The Eosinophil-Edema lesion was also seen in many cases of classical appendicitis in non-suppurative areas where neutrophils were sparse or absent. We hypothesize that this lesion is an allergic response and is probably an early event in the evolution of acute phlegmonous appendicitis. Acute eosinophilic appendicitis may merely be those cases that do not proceed on to suppuration.


[Analysis of knee arthroscopic findings in rheumatic diseases].
46 patients with knee joint arthritis were subjected to arthroscopic examination. The results were analyzed and its clinical significance was discussed. The postoperative diagnoses were rheumatoid arthritis in 19 cases, Sjögren syndrome in one, seronegative spondyloarthropathy in 4, gouty arthritis in one, tuberculous arthritis in one, pigmented villous nodular synovitis in two, undefined synovitis in 5, osteoarthritis in 8 and nonsynovitis conditions in 5. The most important indication of arthroscopic examination is for differential diagnosis of arthritis of unknown cause, such as rheumatoid arthritis with single knee joint involvement, osteoarthritis with symmetric large and small joints involvement as well as crystal induced arthritis. These conditions showed under arthroscope their special features in synovium both grossly, microscopically and immuno-pathologically. The synovial damage as observed through arthroscopic examination correlated to certain extent with the X-ray film changes of the knee joint, but direct visualization with the former is better than indirect imaging with the latter.


Practical management of immune-related adverse events from immune checkpoint protein antibodies for the oncologist.
Monoclonal antibodies directed against immune checkpoint proteins, such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) or programmed death-1 (PD-1), can boost endogenous immune responses directed against tumor cells. Recently, ipilimumab was approved by the U.S. Food and Drug Administration (FDA) for the treatment of metastatic melanoma, and the anti-PD-1 antibody BMS-936558 has shown promising results in patients with melanoma, non-small cell lung cancer, and renal cell cancer. During treatment with these antibodies, a unique set of toxicities occur called immune-related adverse events (irAEs). These irAEs may occur at any time during treatment and include colitis characterized by a mild to moderate but occasionally severe and persistent diarrhea. Hypophysitis, hepatitis, pancreatitis, iridocyclitis, lymphadenopathy, neuropathies, and nephritis have also been reported with ipilimumab, and a subset of those side effects has also been observed with BMS-936558. Patient and physician education as well as good patient-caretaker communication are keys to limiting the morbidity of irAEs. Early recognition of these irAEs and initiation of treatment are critical to reduce the risk of complications, since virtually all irAEs are reversible with the use of steroids and other immune suppressants. The onset of grade 3 to 4 irAEs correlated with treatment response in some ipilimumab studies. This article provides detailed description and recommendations for practicing oncologists to manage the common irAEs associated with antibodies against immune checkpoint blockade.


Pediatric update #10. Treatment of displaced supracondylar fractures of the humerus in children by closed reduction and percutaneous pinning.
In a retrospective study of 25 displaced supracondylar fractures of the humerus in children, treatment by closed reduction and percutaneous pin fixation was reviewed. Follow-up averaged 16 months. Loss of elbow motion and carrying angle were graded according to Flynn's criteria. Twenty-two patients' results were rated excellent, two were good, none was fair, and one was poor. There were no complications reported. Comparison of the values of Baumann's angle obtained from intraoperative, postreduction roentgenograms with those of the opposite, normal elbows predicted the final carrying angles within two degrees in 14 of 17 cases and within five degrees in all 17 cases where such comparison was possible. We conclude that this technique is safe and effective and recommend the use of Baumann's angle as a standard to judge the quality of reduction.


Evidence for Ionic Liquid Gate-Induced Metallization of Vanadium Dioxide Bars over Micron Length Scales.
It has recently been shown that the metal-insulator transition in vanadium dioxide epitaxial films can be suppressed and the material made metallic to low temperatures by ionic liquid gating due to migration of oxygen. The gating is only possible on certain crystal facets where volume channels along the VO2's rutile c-axis intersect the surface. Here, we fabricate bars with the c-axis in plane and oriented parallel to or perpendicular to the length of the bars. We show that only bars with the c-axis perpendicular to the bars, for which the volume channels are accessible from the sides of the bar, can be metallized by ionic liquid gating. Moreover, we find that bars up to at least 0.5 μm wide can be fully gated, demonstrating the possibility of the electric field induced migration of oxygen over very long distances, ∼5 times longer than previously observed.


Cost-effectiveness analysis of a silver-coated endotracheal tube to reduce the incidence of ventilator-associated pneumonia.
To conduct a cost-effectiveness analysis of the economic outcomes of ventilator-associated pneumonia (VAP) prevention associated with silver-coated endotracheal tubes versus uncoated endotracheal tubes. We used a simple decision model based on a hypothetical 1,000-patient cohort intubated with silver-coated or uncoated endotracheal tubes. The primary end point was marginal hospital savings per case of VAP prevented (savings from using silver-coated endotracheal tubes minus acquisition cost divided by number of VAP cases prevented). We followed each branch of the decision model to VAP or no VAP and conducted Monte Carlo simulations and sensitivity analyses. Inputs for VAP incidence, relative risk reduction, and hospital costs were derived from publicly available sources. Relative risk reduction was derived from the pivotal study of the silver-coated endotracheal tube. In the base-case analysis, we reduced the pivotal study relative risk in incidence of microbiologically confirmed VAP in patients intubated 24 hours from 35.9% to 24%. Thus, 23 of 97 expected cases of VAP could be prevented with silver-coated endotracheal tubes. The savings per case of VAP prevented was $12,840 in the base case, with assumed marginal VAP cost of $16,620 and costs of $90.00 for coated and $2.00 for uncoated endotracheal tubes. Estimates were most sensitive to assumptions regarding VAP cost and relative risk reduction with silver-coated endotracheal tubes. Nonetheless, in multivariate sensitivity analyses, the silver-coated endotracheal tubes yielded persistent savings (95% confidence interval, $9,630-$16,356) per case of VAP prevented. With other base-case inputs held constant, break-even cost for silver-coated endotracheal tubes was $388. The silver-coated endotracheal tube represents a strategy for preventing VAP that may yield hospital savings.


The history and enduring contributions of planarians to the study of animal regeneration.
Having an almost unlimited capacity to regenerate tissues lost to age and injury, planarians have long fascinated naturalists. In the Western hemisphere alone, their documented history spans more than 200 years. Planarians were described in the early 19th century as being 'immortal under the edge of the knife', and initial investigation of these remarkable animals was significantly influenced by studies of regeneration in other organisms and from the flourishing field of experimental embryology in the late 19th and early 20th centuries. This review strives to place the study of planarian regeneration into a broader historical context by focusing on the significance and evolution of knowledge in this field. It also synthesizes our current molecular understanding of the mechanisms of planarian regeneration uncovered since this animal's relatively recent entrance into the molecular-genetic age.


Determination of a standard site for the measurement of bone mineral density of the human calcaneus.
Ultrasound of the calcaneus may be used as a cheap, ionising radiation-free and easy to use indicator of skeletal status, and hence of osteoporotic fracture risk. At present ultrasound is not widely used as it suffers from high precision errors. As ultrasound parameters are determined in part by bone mineral density (BMD), an increase in the accuracy and precision of BMD measurements should reduce the precision error associated with ultrasound measurements. The aim of this study was to define an anatomical site on the calcaneus at which accurate and precise measurements of BMD can be made. Ten dry calcanei and 10 cadaveric feet were scanned using a DXA scanner; 9 anatomically defined regions (1 cm2) were selected in the posterior part of the calcaneus for analysis. The centre of region 1 was positioned halfway along the line joining the anterior border of the calcaneal tubercle and the peak of the posterior superior tubercle, and the remaining 8 regions were placed around this central area. The BMD in these 9 regions was compared with the whole bone BMD and the variability of BMD within each of the 9 regions was measured. The reproducibility of the technique was assessed by taking 10 repeated measurements of 2 bone and 2 cadaveric specimens, each specimen being removed and repositioned between measurements. Region 1 was found to be the most representative of total BMD in cadaveric feet. This region also showed the least variability of BMD and consistently gave the lowest coefficients of variation in the reproducibility study both in the bone and the cadaveric specimens. This region is hence the most suitable site on the calcaneus for measuring absolute values of and changes in BMD. The surface position of region 1 was found to be consistently 5/9 along the line at 45 degrees to the vertical, from the lateral malleolus to the heel. The identification of the surface location of region 1 relative to anatomical landmarks of the foot has enabled the same anatomical site to be measured in all subjects. This allows meaningful intersubject comparisons to be made. Preliminary data suggest that precision errors using ultrasound are also reduced when measurements are taken at this region of the calcaneus. The reduction in the precision error of ultrasound assessment of skeletal status may provide a cheap and safe way to identify individuals at risk from osteoporotic fracture.


Colorectal neoplasia in juvenile polyposis or juvenile polyps.
Juvenile (retention) polyps are usually solitary lesions in the colorectum but may be multiple in juvenile polyposis. The association between juvenile polyps and colorectal neoplasia is controversial. We present three patients with juvenile polyposis who had colorectal adenomas or adenomatous epithelium in juvenile polyps at ages 3, 4, and 7 years. In a retrospective study of 57 additional patients with one or more juvenile polyps, 10 patients (18%) had colorectal neoplasia including three with adenocarcinoma, two with tubular adenoma, and six with adenomatous epithelium in a juvenile polyp (one had both adenomatous epithelium and an adenocarcinoma). Nine of these 10 patients had juvenile polyposis defined by the presence of at least three juvenile polyps; and eight of the nine had a family history of juvenile polyps. Colorectal neoplasia occurred at young age (mean (SEM) 37 (5) years). Our findings suggest that patients with juvenile polyps who have three or more juvenile polyps or a family history of juvenile polyps should undergo surveillance for colorectal neoplasia.


Experiences in Sensor-Augmented Pump Therapy in Families with two Children with Type 1 diabetes: A Qualitative Study.
Caring for a child with type 1 diabetes is a tremendous challenge for a family. The aim of the study was to explore the experiences of transition to sensor-augmented pump therapy (SAP) in families with 2 affected children and the internal and external conditions which potentially impede or facilitate the adjustment process. 5 families (9 parents, 8 children and adolescents) who used the SAP technology for 6 months were interviewed to describe their experiences. The interviews were analysed using thematic content analysis. Qualitative analysis of the transcribed interviews revealed that the adaptation process to SAP consisted of several phases and differed among families. There were benefits as well as hassles of using SAP with regard to managing the diabetes, and psychosocial issues: school and peer relations, as well as family relations. While parents clearly regarded the improved metabolic control and hypoglycaemic safety as the most important benefits of SAP, the hassles reported as most important covered a wide range, from technical problems of the system to family conflicts. On the whole, families rated the experience of using SAP as a positive one, with most recommending SAP to other families as long as they were willing to come to terms with the technology and commit to the work and time involved. Sensor-augmented pump therapy can be extremely beneficial and a resource for families who care for more than one child with diabetes. During the adaptation process there is a great need of education and frequent follow-up e. g., by telemedical support.


Clinical Characteristics of Lichen Amyloidosis Associated with Atopic Dermatitis: A Single Center, Retrospective Study.
Lichen amyloidosis is a chronic pruritic skin disorder associated with atopic dermatitis, however, the pathogenetic link between these two conditions remains to be elucidated. Only limited research has been performed on patients diagnosed with both pruritic dermatological conditions. This study aimed to analyze the clinical features of lichen amyloidosis associated with atopic dermatitis. We conducted a matched case-control study of incident lichen amyloidosis with atopic dermatitis between March 2020 and February 2022. Among the 2,481 patients with atopic dermatitis, 20 patients diagnosed with lichen amyloidosis and atopic dermatitis were included as case patients, and 20 patients diagnosed with atopic dermatitis were enrolled as controls. The controls were matched to cases (1:1) by age and sex. We retrospectively reviewed the medical records of the patients. The prevalence of lichen amyloidosis associated with atopic dermatitis was approximately 0.8%, with a male:female sex ratio of 2.33:1. The recorded onset of lichen amyloidosis associated with atopic dermatitis was more common in adult patients, with moderate-to-severe atopic dermatitis. Lichen amyloidosis lesions in patients with atopic dermatitis were most commonly found on the extremities, sparing the head and neck region. The presence of lichen amyloidosis had no significant impact on severity of atopic dermatitis. In patients with lichen amyloidosis associated with atopic dermatitis, the clinical manifestations of lesions are similar to those of conventional lichen amyloidosis lesions in terms of morphology and regional distribution. Further research is required to elucidate the link between the pathogenesis of these two pruritic dermatological conditions.


Acute circulatory effects of dopamine in patients with pulmonary hypertension.
Twenty-one patients, 11 with normal pulomonary artery pressures and 10 with pulmonary hypertension, had haemodynamic measurements performed before and during dopamine infusion while undergoing cardiac catheterization, in order to evaluate the circulatory effects of dopamine in pulmonary hypertension. In both groups on average, heart rate, pulmonary artery mean pressure, aortic mean pressure, and cardiac index increased significantly, while systemic vascular resistance fell significantly during dopamine administration. In neither group did the average pulmonary vascular resistance or right ventricular end-diastolic pressure change significantly. We conclude that dopamine is a safe and potentially useful drug for the treatment of reduced cardiac output, even in patients with pulmonary hypertension.


Ice-Water Immersion and Cold-Water Immersion Provide Similar Cooling Rates in Runners With Exercise-Induced Hyperthermia.
OBJECTIVE: To assess whether ice-water immersion or cold-water immersion is the more effective treatment for rapidly cooling hyperthermic runners. DESIGN AND SETTING: 17 heat-acclimated highly trained distance runners (age = 28 +/- 2 years, height = 180 +/- 2 cm, weight = 68.5 +/- 2.1 kg, body fat = 11.2 +/- 1.3%, training volume = 89 +/- 10 km/wk) completed a hilly trail run (approximately 19 km and 86 minutes) in the heat (wet-bulb globe temperature = 27 +/- 1 degrees C) at an individually selected "comfortable" pace on 3 occasions 1 week apart. The random, crossover design included (1) distance run, then 12 minutes of ice-water immersion (5.15 +/- 0.20 degrees C), (2) distance run, then 12 minutes of cold-water immersion (14.03 +/- 0.28 degrees C), or (3) distance run, then 12 minutes of mock immersion (no water, air temperature = 28.88 +/- 0.76 degrees C). MEASUREMENTS: Each subject was immersed from the shoulders to the hip joints for 12 minutes in a tub. Three minutes elapsed between the distance run and the start of immersion. Rectal temperature was recorded at the start of immersion, at each minute of immersion, and 3, 6, 10, and 15 minutes postimmersion. No rehydration occurred during any trial. RESULTS: Length of distance run, time to complete distance run, rectal temperature, and percentage of dehydration after distance run were similar (P >.05) among all trials, as was the wet-bulb globe temperature. No differences (P >.05) for cooling rates were found when comparing ice-water immersion, cold-water immersion, and mock immersion at the start of immersion to 4 minutes, 4 to 8 minutes, and the start of immersion to 8 minutes. Ice-water immersion and cold-water immersion cooling rates were similar (P >.05) to each other and greater (P <.05) than mock immersion at 8 to 12 minutes, the start of immersion to 10 minutes, and the start of immersion to every other time point thereafter. Rectal temperatures were similar (P >.05) between ice-water immersion and cold-water immersion at the completion of immersion and 15 minutes postimmersion, but ice-water immersion rectal temperatures were less (P <.05) than cold-water immersion at 6 and 10 minutes postimmersion. CONCLUSIONS: Cooling rates were nearly identical between ice-water immersion and cold-water immersion, while both were 38% more effective in cooling after 12 minutes of immersion than the mock-immersion trial. Given the similarities in cooling rates and rectal temperatures between ice-water immersion and cold-water immersion, either mode of cooling is recommended for treating the hyperthermic individual.


Declines in Physical Activity among New Zealand Adults during the COVID-19 Pandemic: Longitudinal Analyses of Five Data Waves from Pre-Pandemic through April 2021.
Insights specific to the impact of the COVID-19 pandemic on physical activity participation in New Zealand (NZ) is limited. The purpose of this study was to examine longitudinal changes in leisure-time physical activity from pre-pandemic through April 2021. Demographic characteristics (age, gender, ethnicity, deprivation, disability status) and numerous indicators of leisure-time physical activity participation were assessed in a cohort of NZ adults (n = 1854, 54.6% women) over five waves (pre-pandemic, April 2020, June 2020, September 2020, and April 2021). Repeat measures were completed for: proportion participating in any physical activity; proportion meeting aerobic physical activity recommendations; physical activity duration; number of physical activities. There was a significant (p < 0.05) decline in mean physical activity duration and number of activities during the initial lockdown period in April 2020, but the proportion participating in any physical activity and the proportion meeting physical activity recommendations remained stable. However, all four physical activity participation indicators were significantly (p < 0.05) below pre-pandemic levels in all subsequent waves. Considerable and sustained declines in NZ adult leisure-time physical activity participation were evident over the first year of the pandemic. As of April 2021, physical activity participation showed limited signs of recovering to pre-pandemic levels.


[Compliance with the metabolic goals in diabetes mellitus treatment in the rural area of Ourense, Spain].
To evaluate the degree to which the metabolic check-up objectives among Type II diabetes patients were met in rural primary care by comparing them to the values recommended by the American Diabetes Association (ADA) and the Diabetes in Primary Care Study Group (GEDAPS). Descriptive cross-sectional study. A sample size was calculated based on the glycosolated hemoglobin (HbA1c) test in 119 individuals. A total of 253 patients with Type II diabetes followed up for at least two years at their healthcare facility took part. The patients in question were selected at random from among 17 medical lists at 11 rural healthcare facilities in the province of Ourense (Spain). Demographic variables, cardiovascular risk factors, pharmacological treatment, self-analyses, eye fundus, tactile sensitivity, HbA1c, lipid profile, blood pressure and body mass index data were taken from the patients' clinical records. A total of 44.3% of those in the sample had undergone an HbA1c test within the immediately prior six-month period, showing a value of under seven percent (7%). A total of 21.2% had a blood pressure of under 130/80, and 19.8% a LDL cholesterol level of under 100 mg/dl. A total of 40.7% of those patients with a LDL cholesterol level over 100 were not undergoing any hypolipemiant treatment. A total of 20.4% of the patients showing high blood pressure readings were not undergoing any blood pressure lowering treatment. On the basis of these three factors, a total of 2.5% met the check-up objectives. Thirty-six percent (36%) were antiaggregated with AAS. A major deficit is revealed both in the frequency of the check-ups conducted by the healthcare professionals as well as the number of interventions performed for achieving the proposed objectives, showing results far below what is recommended in the clinical practice guidelines.


The microstructure of colonies of the Connaught BCG strain.
It has previously been shown that there is a certain correlation between the biological properties of BCG strains-properties on which their immunogenicity and allergenicity depend-and the macroscopic appearance of the growth of these colonies on solid and liquid media. To investigate this phenomenon in greater detail, the author examined the microstructure of colonies of the Connaught BCG strain grown on both solid and liquid media. Colonies were fixed in agar, embedded in paraffin, sectioned and stained by the Ziehl-Neelsen technique.A striking finding was the alternation of acid-fast and non-acid-fast zones in colonies grown on bovine-serum agar or Ogawa egg medium; the strata nearest the surface of the solid media were usually more acid-fast than were the deeper strata. Colonies grown in Sula's liquid medium, on the other hand, showed no such stratification and were equally acid-fast at all points. These differences may be the result of genetic factors or of the different nutritional conditions provided by solid and liquid media.


GluR-A-Deficient mice display normal acquisition of a hippocampus-dependent spatial reference memory task but are impaired during spatial reversal.
Acquisition and reversal of a spatial discrimination were assessed in an appetitive, elevated plus-maze task in 4 groups of mice: knockout mice lacking the AMPA receptor subunit GluR-A (GluR1), wild-type controls, mice with cytotoxic hippocampal lesions, and controls that had undergone sham surgery. In agreement with previous studies using tasks such as the water maze, GluR-A(-/-) mice were unimpaired during acquisition of the spatial discrimination task, whereas performance in the hippocampalgroup remained at chance levels. In contrast to their performance during acquisition, the GluR-A(-/-) mice displayed a mild deficit during reversal of the spatial discrimination and were profoundly impaired during discrete trial, rewarded-alternation testing on the elevated T maze. The latter result suggests a short-term, flexible spatial working memory impairment in GluR-A(-/-) mice, which might also underlie their mild deficit during spatial reversal.


Identification of suitable endogenous control genes for microRNA gene expression analysis in human breast cancer.
The discovery of microRNAs (miRNAs) added an extra level of intricacy to the already complex system regulating gene expression. These single-stranded RNA molecules, 18-25 nucleotides in length, negatively regulate gene expression through translational inhibition or mRNA cleavage. The discovery that aberrant expression of specific miRNAs contributes to human disease has fueled much interest in profiling the expression of these molecules. Real-time quantitative PCR (RQ-PCR) is a sensitive and reproducible gene expression quantitation technique which is now being used to profile miRNA expression in cells and tissues. To correct for systematic variables such as amount of starting template, RNA quality and enzymatic efficiencies, RQ-PCR data is commonly normalised to an endogenous control (EC) gene, which ideally, is stably-expressed across the test sample set. A universal endogenous control suitable for every tissue type, treatment and disease stage has not been identified and is unlikely to exist, so, to avoid introducing further error in the quantification of expression data it is necessary that candidate ECs be validated in the samples of interest. While ECs have been validated for quantification of mRNA expression in various experimental settings, to date there is no report of the validation of miRNA ECs for expression profiling in breast tissue. In this study, the expression of five miRNA genes (let-7a, miR-10b, miR-16, miR-21 and miR-26b) and three small nucleolar RNA genes (RNU19, RNU48 and Z30) was examined across malignant, benign and normal breast tissues to determine the most appropriate normalisation strategy. This is the first study to identify reliable ECs for analysis of miRNA by RQ-PCR in human breast tissue.


Polypyrrole-coated poly(l-lactic acid-co-ε-caprolactone)/silk fibroin nanofibrous membranes promoting neural cell proliferation and differentiation with electrical stimulation.
Polypyrrole (Ppy), as a conductive polymer, is commonly used for nerve tissue engineering because of its good conductivity and non-cytotoxicity. To avoid the inconvenience of Ppy processing, it was coated on electrospun poly(l-lactic acid-co-ε-caprolactone)/silk fibroin (PLCL/SF) nanofibers via the in situ oxidative polymerization of pyrrole monomers in this study. Ppy-coated PLCL/SF membranes were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and thermogravimetric (TG) analysis. The results confirmed the disposition of Ppy on the PLCL/SF nanofibers, and the nanofibers kept their nanofibrous morphology and thermal stability, in comparison to the untreated ones. The conductivities and water contact angles were evaluated as well, and indicated that the conductivity and hydrophilicity of Ppy-coated nanofibers were increased. Furthermore, this study showed that electrical stimulation (ES) promoted PC12 cell differentiation and axonal extension on Ppy-coated nanofibers. The MTT assay suggested that both Ppy and ES could promote Schwann cell (SC) proliferation. Immunofluorescence staining and real time-qPCR (RT-qPCR) testing demonstrated that ES could induce PC12 cell differentiation even without nerve growth factor (NGF) treatment, and moreover, Ppy coating increased the inducing effects on PC12 cell differentiation. The overall results indicated the promising potential of Ppy-coated PLCL/SF nanofibrous membranes for peripheral nerve repair and regeneration.


The structure of reduced tryparedoxin peroxidase reveals a decamer and insight into reactivity of 2Cys-peroxiredoxins.
Tryparedoxin peroxidase (TryP) is a recently discovered 2Cys-peroxiredoxin involved in defence against oxidative stress in parasitic trypanosomatids. The crystal structure of recombinant Crithidia fasciculata TryP, in the reduced state, has been determined using multi-wavelength anomalous dispersion methods applied to a selenomethionyl derivative. The model comprises a decamer with 52 symmetry, ten chloride ions with 23 water molecules and has been refined, using data to 3.2 A resolution (1 A=0.1 nm), to an R-factor and R(free) of 27.3 and 28.6 %, respectively. Secondary structure topology places TryP along with tryparedoxin and glutathione peroxidase in a distinct subgroup of the thioredoxin super-family. The molecular details at the active site support ideas about the enzyme mechanism and comparisons with an oxidised 2Cys-peroxiredoxin reveal structural alterations induced by the change in oxidation state. These include a difference in quaternary structure from dimer (oxidised form) to decamer (reduced form). The 2Cys-peroxiredoxin assembly may prevent indiscriminate oligomerisation, localise ten peroxidase active sites and contribute to both the specificity of reduction by the redox partner tryparedoxin and attraction of peroxides into the active site.


[Women and their careers at Unicamp's Faculty of Medical Sciences: unique voices and collective images].
This article presents a historical and social rediscovery of the trajectories of women professors at Unicamp's Faculty of Medical Sciences and of their personal and professional choices, in conjunction with their social strategies. It explores their roles and positions in the academic world, how they shaped their habitus, and how the latter related to the gender issue. The theoretical reference for the qualitative methodology employed was taken from studies of gender and of the sociology of science and health, including Merton's focused interviews and Bardin's content analysis. The women identified social representations of family, marriage, and children, the social division of work time, and the patriarchal structure of science as gender elements that influenced their careers.


Distorted payment system undermines business case for health quality and efficiency gains.
Efforts to improve the efficiency and quality of health care are unlikely to be successful if physicians and hospitals incur steep financial losses from success in accomplishing these goals, according to a new study by the Center for Studying Health System Change (HSC). Currently, most efforts to improve efficiency for a specific medical condition usually reduce the number of services per patient that can be billed, posing financial challenges for providers. These challenges are often magnified by the current fee-for-service payment structure, where some services are highly profitable and others are unprofitable, further undermining the case for redesigning care delivery to improve quality and efficiency. These dynamics are seen in the collaboration between Virginia Mason Medical Center (VMMC) and Aetna in Seattle to improve care for four common conditions. Although Aetna and participating self-insured employers have agreed to pay higher rates for certain unprofitable services if reductions in use of profitable services are achieved, VMMC still faces a financial challenge from applying more efficient care practices to patients covered by other insurers.


The dental caries experience of 11-year-old children in Great Britain. Surveys coordinated by the British Association for the Study of Community Dentistry in 2004 / 2005.
This paper reports the results of standardized clinical caries examinations of 11-year-old children from across England and Wales, Scotland, Isle of Man, and Jersey in 2004/5. These co-ordinated surveys are the latest in a series which seek to monitor the dental health of children and to assess the delivery of dental services. The criteria and conventions of the British Association for the Study of Community Dentistry were used. Representative samples were drawn from participating strategic health authorities (SHAs), primary care trusts (PCTs), health boards (HBs), and local health boards (LHBs). Caries was diagnosed at the caries into dentine threshold using a visual method without radiography or fibre-optic transillumination. The results again demonstrated a wide variation in disease prevalence and care strategies across Great Britain. Mean values for D3MFT within the current English strategic health authorities ranged from 0.19 in Harlow to 1.32 in North Manchester and in Salford; in Wales mean values ranged from 0.69 in Vale of Glamorgan to 2.09 in Blaenau Gwent; while in Scotland they ranged from 0.59 in Orkney to 1.77 in Western Isles. Mean D3MFT across England was 0.64 (D3T = 0.32, MT = 0.06, FT = 0.25), across Wales it was 1.09 (D3T = 0.48, MT 0.11, FT = 0.50), and across Scotland values were 1.29 (D3T = 0.52, MT = 0.17, FT = 0.60). Overall, 31.3% of children in England & Wales and 47.1% of children inspected in Scotland had evidence of caries experience in dentine (D3MFT > 0, including visual dentine caries). As in previous surveys, the distribution of caries was highly skewed. Thus the mean caries experience for those with dentinal decay in England and Wales was 2.12, as opposed to the overall mean of 0.66; in Scotland the corresponding values were 2.74 and 1.29. Trends over time demonstrate an improvement in overall mean D3MFT for England and Wales since the 2000/2001 of 12-year-olds, although part of this difference is accountable to the younger age, at examination, in this survey. The mean value for those with dentine decay experience was also marginally less at 2.12 compared with 2.35 in the previous survey. (Figures for Scotland were not included in the 2000/2001 survey.) The care index was also found to be marginally lower than previously at 41% compared with 48% but again the younger age of the children would influence this value. Dental health of 11-year-old children has been surveyed in Great Britain, Jersey, and the Isle of Man: being a slightly younger mean age than in previous BASCD surveys. Geographic variation in oral health is marked at both the local and national levels. Overall, the provision of operative care for those with dentinal decay is around 42%. While many children enjoy good oral health, sizable groups remain within the population of 11-year-old children who have a clinically significant burden of preventable dental disease.


Confocal scanning of intervertebral disc cells in 3D: Inside alginate beads and in native microenvironment.
The interaction between cells and their extracellular matrix (ECM) is crucial to maintain both tissue and cellular homeostasis. Indeed, cell phenotype is significantly affected by the 3D microenvironment. Although highly convenient, isolating cells from the intervertebral disc (IVD) and growing them in 2D on plastic or glass substrates, causes them to rapidly lose their phenotype and consequently alter their gene and protein expression. While characterization of cells in their native or simulated 3D environment is preferred, such approaches are complexed by limitations in phenotypic readouts. In the current article, we describe a detailed protocol to study nucleus pulposus cells in 3D-embedded in alginate as a permeable cell-staining reservoir, as well as adaptation for cell staining and imaging in their native ECM. This method allows for detection of phenotypical and cytoskeletal changes in cells within native tissue or 3D alginate beads using confocal microscopy, without the need for histological processing.


Mortality in patients with celiac disease.
Celiac disease is an autoimmune disorder triggered by ingestion of gluten-containing foods. Epidemiologic studies dating from the 1950s established its association with gastrointestinal malignancies, particularly small bowel lymphoma. Corrao et al. recently demonstrated that patients with celiac disease are at increased risk of mortality. Further, this risk is directly related to compliance with a gluten-free diet. Continued research is needed regarding the development of malignant complications related to celiac disease.


Effective treatment of advanced multiple myeloma refractory to alkylating agents.
Twenty-nine patients with advanced refractory multiple myeloma were treated with intermittent high-dose dexamethasone in combination with four-day infusions of vincristine and doxorubicin. Rapid and marked tumor-mass reduction (greater than 75 per cent) was noted in 14 of 20 patients whose disease was resistant to alkylating agents and in 3 of 9 patients with additional resistance to doxorubicin--a result far superior to those in previous trials with similar patients. In responsive patients, remissions were of excellent quality, and survival was significantly longer than in unresponsive patients.


NOHA: A Promising Biomarker for Determining Estrogen Receptor Status Among Patients With Breast Cancer in Resource-Constrained Settings.
Challenges to breast cancer control in low-and middle-income countries exist because of constrained access to care, including pathology services. Immunohistochemistry (IHC)-based estrogen receptor (ER) analysis is limited-nonexistent because of few and inadequately staffed and equipped pathology laboratories. We have identified Nw-hydroxy-L-Arginine (NOHA) as a blood-based biomarker to distinguish ER status in US patients with breast cancer. Here, we examine NOHA's clinical utility as an ER IHC alternative in Tanzanian patients. Following informed consent, 70 newly diagnosed, known or suspected patients with breast cancer were enrolled at Kilimanjaro Christian Medical Center; basic, deidentified clinical and sociodemographic data were collected. For each, a needle prick amount of blood was collected on a Noviplex plasma card and stored at -80°C. Plasma cards and unstained tumor pathology slides were shipped regularly to US laboratories for NOHA, histologic and IHC analysis. NOHA and IHC assay operators were blinded to each other's result and patient clinical status. Paired NOHA and IHC results were compared. Slides from 43 participants were available for pathological analysis in the United States. Of those with confirmed malignancy (n = 39), 44%, 51%, 5% were ER-positive, ER-negative, and ER inconclusive, respectively. NOHA levels were available among 33 of 43 of those with pathological data and showed distinct threshold levels correlating 100% to tumor ER IHC and disease categorization where a level below 4 nM, from 4 to 8 nM, and above 8 nM signified ER-negative, ER-positive, and no cancer, respectively. The results are consistent with findings from US patients and suggest NOHA's clinical utility as an accessible IHC replacement in determining ER status among low-and middle-income country patients with breast cancer, promising to extend access to cost-efficient, available hormonal agents and improve outcomes.


Gene-to-metabolite networks for terpenoid indole alkaloid biosynthesis in Catharanthus roseus cells.
Rational engineering of complicated metabolic networks involved in the production of biologically active plant compounds has been greatly impeded by our poor understanding of the regulatory and metabolic pathways underlying the biosynthesis of these compounds. Whereas comprehensive genome-wide functional genomics approaches can be successfully applied to analyze a select number of model plants, these holistic approaches are not yet available for the study of nonmodel plants that include most, if not all, medicinal plants. We report here a comprehensive profiling analysis of the Madagascar periwinkle (Catharanthus roseus), a source of the anticancer drugs vinblastine and vincristine. Genome-wide transcript profiling by cDNA-amplified fragment-length polymorphism combined with metabolic profiling of elicited C. roseus cell cultures yielded a collection of known and previously undescribed transcript tags and metabolites associated with terpenoid indole alkaloids. Previously undescribed gene-to-gene and gene-to-metabolite networks were drawn up by searching for correlations between the expression profiles of 417 gene tags and the accumulation profiles of 178 metabolite peaks. These networks revealed that the different branches of terpenoid indole alkaloid biosynthesis and various other metabolic pathways are subject to differing hormonal regulation. These networks also served to identify a select number of genes and metabolites likely to be involved in the biosynthesis of terpenoid indole alkaloids. This study provides the basis for a better understanding of periwinkle secondary metabolism and increases the practical potential of metabolic engineering of this important medicinal plant.


Comparative analysis of roxadustat efficacy between maintenance hemodialysis and peritoneal dialysis patients.
This study evaluated the comparative efficacy of roxadustat for renal anemia between patients on maintenance hemodialysis (HD) and peritoneal dialysis (PD). 93 maintenance dialysis patients who regularly followed up from August 2015 to June 2021 were enrolled. Despite receiving a therapeutic dose ≥ 12,000 U/week of erythropoiesis-stimulating agents (E+SA) in the past 12 weeks, this had not worked very well. Subjects were assigned to the HD group (n = 60) or the PD group (n = 33) based on their dialysis treatment modality. All patients received oral roxadustat and were followed up for 24 weeks, after which their hemoglobin, serum iron, transferrin saturation, and ferritin were tested. We observed that the hemoglobin level of PD patients was significantly increased from 76.1 ± 15.7 g/L to 106 ± 23.8 g/L (p < 0 .001), while it significantly increased from 73.8 ± 12.9 g/L to 100.7 ± 20.2 g/L (p < 0.001) in the HD patients. After 1 and 3 months of roxadustat treatment, the hemoglobin level and its change in the PD group was significantly higher compared to that in the HD group despite the higher dose of roxadustat in the latter group. In addition, roxadustat was noted to reduce cholesterol levels and stabilize serum iron levels in parallel with improving hemoglobin levels. Roxadustat can effectively increase the hemoglobin level of maintenance dialysis patients, even in those with low erythropoietin response or erythropoietin resistance, and, more importantly, its efficacy in PD patients was more significant.


Virus-Host Interactions: New Insights and Advances in Drug Development Against Viral Pathogens.
Viruses are the most devastating pathogens of almost all life forms including humans and animals. Viruses can replicate very fast and may affect any metabolic and physiological function of the host cell. Therefore, it has been a challenge to develop a universal and common treatment against viral pathogens, in contrast to bacterial pathogens. Virus-host interaction is a complex phenomenon and often is virus- and host cell-specific. Exciting new insights into the molecular pathogenesis and host-virus interactions have been gained over the past few decades. These advances have enabled researchers to design better antiviral drugs. The literature related to various aspects of virus-host interactions: new insights and advances in drug development was collected from several scientific research related databases such as Science Direct, Google Scholar, Scopus, PubMed, AGRICOLA, and Medline, etc. Total number of 319 research papers was used to compile the information regarding drug development against viral pathogens. Clinical adequacy of antiviral drugs and their bioavailability are important parameters for effective treatment of viral infections. The problems associated with effective delivery of a drug in a safe and desired quantity have led to the search for (and design of) better drug delivery systems. In recent past, several new antiviral drugs have been developed, which have high therapeutic effectiveness against life-threatening viral diseases such as HIV, hepatitis B virus, herpes virus, dengue virus and influenza virus infections. The majority of recent advances in antiviral drug discovery were possible due to the developments in allied fields such as in vitro virus cultivation technology, molecular biology of viral-genome-encoded enzymes, complete-genome-sequence-based studies of viruses and identification of suitable targets for antiviral drugs in viral genomes. Recently, several novel drug delivery approaches including small interfering RNAs (siRNAs) have emerged to aid antiviral therapy. The present review is aimed at providing an update on research and development efforts being made to create effective antiviral chemotherapeutic agents and approaches to their delivery to appropriate targeted cells or tissues.


New application for expanded porphyrins: sapphyrin and heterosapphyrins as inhibitors of Leishmania parasites.
Sapphyrins and a series of related porphyrinoid macrocycles have been investigated as potential agents for the treatment of leishmaniasis. The effectiveness of the compounds was evaluated in vitro upon incubation with Leishmania tarentolae or L. panamensis amastigotes and promastigotes. Their effectiveness was also assessed against intracellular L. panamensis. The cytotoxicity of the compounds was evaluated in vitro using the U937 human promonocyte cell line. Effectiveness and cytotoxicity were assessed in the presence and absence of visible light to assess the photodynamic activity of the compounds. Sapphyrin and two related heterosapphyrins were shown to be particularly effective as inhibitors of Leishmania. A photodynamic effect was observed, which may be attributed to the formation of reactive oxygen species. Yields of singlet oxygen ((1)O(2)) produced were determined in ethanol solutions by direct measurement of (1)O(2) phosphorescence. Confocal microscopy demonstrated that sapphyrin and related macrocycles were taken up by the Leishmania cells and that their presence induces the formation of mitochondrial superoxide. Sapphyrins have been widely investigated as anticancer agents and we here show activity against the Leishmania parasites.


Maternal immune responses to trophoblast: the contribution of the horse to pregnancy immunology.
The horse has proven to be a distinctively informative species in the study of pregnancy immunology for several reasons. First, unique aspects of the anatomy and physiology of the equine conceptus facilitate approaches that are not possible in other model organisms, such as non-surgical recovery of early stage embryos and conceptuses and isolation of pure trophoblast cell populations. Second, pregnant mares make strong cytotoxic antibody responses to paternal major histocompatibility complex class I antigens expressed by the chorionic girdle cells, permitting detailed evaluation of the antigenicity of these invasive trophoblasts and how they affect the maternal immune system. Third, there is abundant evidence for local maternal cellular immune responses to the invading trophoblasts in the pregnant mare. The survival of the equine fetus in the face of strong maternal immune responses highlights the complex immunoregulatory mechanisms that result in materno-fetal tolerance. Finally, the parallels between human and horse trophoblast cell types, their gene expression, and function make the study of equine pregnancy highly relevant to human health. Here, we review the most pertinent aspects of equine reproductive immunology and how studies of the pregnant mare have contributed to our understanding of maternal acceptance of the allogeneic fetus.


Video Confirmation of Head Impact Sensor Data From High School Soccer Players.
Recent advances in technology have enabled the development of head impact sensors, which provide a unique opportunity for sports medicine researchers to study head kinematics in contact sports. Studies have suggested that video or observer confirmation of head impact sensor data is required to remove false positives. In addition, manufacturer filtering algorithms may be ineffective in identifying true positives and removing true negatives. To (1) identify the percentage of video-confirmed events recorded by headband-mounted sensors in high school soccer through video analysis, overall and by sex; (2) compare video-confirmed events with the classification by the manufacturer filtering algorithms; and (3) quantify and compare the kinematics of true- and false-positive events. Cohort study; Level of evidence, 2. Adolescent female and male soccer teams were instrumented with headband-mounted impact sensors (SIM-G; Triax Technologies) during games over 2 seasons of suburban high school competition. Sensor data were sequentially reduced to remove events recorded outside of game times, associated with players not on the pitch (ie, field) and players outside the field of view of the camera. With video analysis, the remaining sensor-recorded events were identified as an impact event, trivial event, or nonevent. The mechanisms of impact events were identified. The classifications of sensor-recorded events by the SIM-G algorithm were analyzed. A total of 6796 sensor events were recorded during scheduled varsity game times, of which 1893 (20%) were sensor-recorded events associated with players on the pitch in the field of view of the camera during verified game times. Most video-confirmed events were impact events (n = 1316, 70%), followed by trivial events (n = 396, 21%) and nonevents (n = 181, 10%). Female athletes had a significantly higher percentage of trivial events and nonevents with a significantly lower percentage of impact events. Most impact events were head-to-ball impacts (n = 1032, 78%), followed by player contact (n = 144, 11%) and falls (n = 129, 10%) with no significant differences between male and female teams. The SIM-G algorithm correctly identified 70%, 52%, and 66% of video-confirmed impact events, trivial events, and nonevents, respectively. Video confirmation is critical to the processing of head impact sensor data. Percentages of video-confirmed impact events, trivial events, and nonevents vary by sex in high school soccer. Current manufacturer filtering algorithms and magnitude thresholds are ineffective at correctly classifying sensor-recorded events and should be used with caution.


COVID-19 Outbreak: An Overview.
In late December 2019, Chinese health authorities reported an outbreak of pneumonia of unknown origin in Wuhan, Hubei Province. A few days later, the genome of a novel coronavirus was released (http://viro-logical.org/t/novel-2019-coronavirus-genome/319; Wuhan-Hu-1, GenBank accession No. MN908947) and made publicly available to the scientific community. This novel coronavirus was provisionally named 2019-nCoV, now SARS-CoV-2 according to the Coronavirus Study Group of the International Committee on Taxonomy of Viruses. SARS-CoV-2 belongs to the Coronaviridae family, Betacoronavirus genus, subgenus Sarbecovirus. Since its discovery, the virus has spread globally, causing thousands of deaths and having an enormous impact on our health systems and economies. In this review, we summarize the current knowledge about the epidemiology, phylogenesis, homology modeling, and molecular diagnostics of SARS-CoV-2. Key Messages: Phylogenetic analysis is essential to understand viral evolution, whereas homology modeling is important for vaccine strategies and therapies. Highly sensitive and specific diagnostic assays are key to case identification, contact tracing, identification of the animal source, and implementation of control measures.


Incorporation of mannose 6-phosphate receptors into liposomes. Receptor topography and binding of alpha-mannosidase.
A receptor that binds the lysosomal enzyme alpha-mannosidase via mannose 6-phosphate moieties (mannose 6-phosphate receptor) was purified from Swarm-rat chondrosarcoma and bovine liver microsomal membranes. Receptor-reconstituted liposomes were prepared by dialysis of taurodeoxycholate-dispersed lipids with purified mannose 6-phosphate receptor. Liposomes appeared by electron microscopy as 60-120 nm unilamellar vesicles. Receptor-reconstituted liposomes retained the ability to bind alpha-mannosidase specifically. Binding was saturable with an apparent Kd of 1 nM and was competitively inhibited by mannose 6-phosphate (Ki 2mM). Liposomes containing entrapped 125I-bovine serum albumin were used to demonstrate that treatment with 0.045% taurodeoxycholate rendered liposomes permeable to macromolecules without solubilizing the membrane. Receptor orientation in the liposome membrane was established by measuring binding of ligand to intact and detergent-treated liposomes. Unlike coated vesicles, which contain cryptic mannose 6-phosphate receptors [Campbell, Fine, Squicciarini & Rome (1983) J. Biol. Chem. 258, 2526-2533], treatment of liposomes with detergent revealed no additional cryptic binding sites. In addition, treatment of liposomes with 0.75% trypsin abolished total receptor binding activity. The results suggest that the receptor is inserted with its binding site facing the outside of the liposome.


Assignment of a single disulphide bridge in human alpha2-antiplasmin: implications for the structural and functional properties.
Human alpha2-antiplasmin (alpha2AP) is a serpin involved in the regulation of blood coagulation. Most serpins, unlike smaller serine proteinase inhibitors, do not contain disulphide bridges. alpha2AP is an exception from this generalization and has previously been shown to contain four Cys residues organized into two disulphide bridges [Lijnen, Holmes, van Hoef, Wiman, Rodriguez and Collen (1987) Eur. J. Biochem. 166, 565-574]. However, we found that alpha2AP incorporates iodo[14C]acetic acid, suggesting that the protein contains reactive thiol groups. This observation prompted a re-examination of the state of the thiol groups, which revealed (i) a disulphide bridge between Cys43 and Cys116, (ii) that Cys76 is bound to a cysteinyl-glycine dipeptide, and (iii) and Cys125 exists as either a free thiol or in a mixed disulphide with another Cys residue. The disulphide identified between Cys43 and Cys116 appears to be conserved in orthologous proteins since the homologous Cys residues form disulphide bonds in bovine and possibly mouse alpha2AP. The conservation of this disulphide bridge suggests that it is important for functional aspects of alpha2AP. However, the structural and functional analysis described in this study does not support this conclusion.


[Biologically active compounds in the mechanism of formation of reflux-nephropathy in children].
A concept is proposed laying emphasis on the involvement of cytokines, growth factors, prostaglandins, and nitrogen oxides in the mechanism of formation of reflux-nephropathy in children. It is shown that enhanced production of mediators of inflammation and humoral growth factors in patients with vesico-ureter reflux depends on the degree of infiltrative and sclerotic changes in the kidneys. The accompanying dysbalance of pro- and anti-inflammatory cytokines due to increased endogeneous production of TNF-alpha and concomitant decrease of daily BL-10 excretion constitutes an unfavourable prognostic factor of reflux-nephropathy. There is evidence that inclusion of ACE inhibitors (Enap) in therapy of vesico-ureter reflux during 6 months leads to a marked improvement of the structural and functional state of the kidneys. It suggests high renoprotective potential of these preparations and the possibility of their use for prophylaxis of nephrosclerosis in children.


Dynamic conformational changes in munc18 prevent syntaxin binding.
The Sec1/munc18 protein family is essential for vesicle fusion in eukaryotic cells via binding to SNARE proteins. Protein kinase C modulates these interactions by phosphorylating munc18a thereby reducing its affinity to one of the central SNARE members, syntaxin-1a. The established hypothesis is that the reduced affinity of the phosphorylated munc18a to syntaxin-1a is a result of local electrostatic repulsion between the two proteins, which interferes with their compatibility. The current study challenges this paradigm and offers a novel mechanistic explanation by revealing a syntaxin-non-binding conformation of munc18a that is induced by the phosphomimetic mutations. In the present study, using molecular dynamics simulations, we explored the dynamics of the wild-type munc18a versus phosphomimetic mutant munc18a. We focused on the structural changes that occur in the cavity between domains 3a and 1, which serves as the main syntaxin-binding site. The results of the simulations suggest that the free wild-type munc18a exhibits a dynamic equilibrium between several conformations differing in the size of its cavity (the main syntaxin-binding site). The flexibility of the cavity's size might facilitate the binding or unbinding of syntaxin. In silico insertion of phosphomimetic mutations into the munc18a structure induces the formation of a conformation where the syntaxin-binding area is rigid and blocked as a result of interactions between residues located on both sides of the cavity. Therefore, we suggest that the reduced affinity of the phosphomimetic mutant/phosphorylated munc18a is a result of the closed-cavity conformation, which makes syntaxin binding energetically and sterically unfavorable. The current study demonstrates the potential of phosphorylation, an essential biological process, to serve as a driving force for dramatic conformational changes of proteins modulating their affinity to target proteins.


Diffusion Kernel Attention Network for Brain Disorder Classification.
Constructing and analyzing functional brain networks (FBN) has become a promising approach to brain disorder classification. However, the conventional successive construct-and-analyze process would limit the performance due to the lack of interactions and adaptivity among the subtasks in the process. Recently, Transformer has demonstrated remarkable performance in various tasks, attributing to its effective attention mechanism in modeling complex feature relationships. In this paper, for the first time, we develop Transformer for integrated FBN modeling, analysis and brain disorder classification with rs-fMRI data by proposing a Diffusion Kernel Attention Network to address the specific challenges. Specifically, directly applying Transformer does not necessarily admit optimal performance in this task due to its extensive parameters in the attention module against the limited training samples usually available. Looking into this issue, we propose to use kernel attention to replace the original dot-product attention module in Transformer. This significantly reduces the number of parameters to train and thus alleviates the issue of small sample while introducing a non-linear attention mechanism to model complex functional connections. Another limit of Transformer for FBN applications is that it only considers pair-wise interactions between directly connected brain regions but ignores the important indirect connections. Therefore, we further explore diffusion process over the kernel attention to incorporate wider interactions among indirectly connected brain regions. Extensive experimental study is conducted on ADHD-200 data set for ADHD classification and on ADNI data set for Alzheimer's disease classification, and the results demonstrate the superior performance of the proposed method over the competing methods.


Synthesis, anticancer activity and docking of some substituted benzothiazoles as tyrosine kinase inhibitors.
Protein tyrosine kinases occupy a central position in the control of cellular proliferation and its inactivation might lead to the discovery of a new generation anticancer compounds. Substituted benzothiazoles have been found to mimic the ATP-competitive binding of genistein and quercetin to tyrosine kinase. A series of novel 2-phenyl-1,3-benzothiazoles were synthesized and characterised by IR, (1)H NMR and mass spectroscopy. All the compounds were tested for their anticancer activity against MCF-7 breast cancer cell line with the MTT assay. Most of the compounds showed moderate to good anti-breast cancer activity. Anticancer activity varied with substitution on the benzothiazole nucleus with halogens and at 4 position, substitution of the 2-phenyl moiety with methyl and methoxy groups was also explored. Among the compounds tested with MTT assay, mono fluoro substitution on benzothiazole nucleus and 4'-methyl variations at 2-phenyl position demonstrated highest percent growth inhibition of MCF-7 cells. Docking studies of the synthesised compounds was done on EGFR using GRIP batch docking method to study their observed activity.


Motor learning outcomes of handrim wheelchair propulsion during active spinal cord injury rehabilitation in comparison with experienced wheelchair users.
To investigate changes in wheelchair propulsion technique and mechanical efficiency across first five weeks of active inpatient spinal cord injury rehabilitation and to compare the outcomes at discharge with experienced wheelchair users with spinal cord injury. Eight individuals with recent spinal cord injury performed six weekly submaximal exercise tests. The first and last measurement additionally contained a wheelchair circuit and peak graded exercise test. Fifteen experienced individuals performed all above-mentioned tests on one occasion. Mechanical efficiency and propulsion technique did not change during the five weeks of inpatient rehabilitation. Peak power output during peak graded test and performance time on the wheelchair circuit improved between the first and the last week. No difference in propulsion technique, peak power output, and performance time was found between the persons with a recent injury and the experienced group. Mechanical efficiency was higher after the correction for the difference in relative power output in the experienced group. The group with a recent injury did not improve mechanical efficiency and propulsion technique over the period of active rehabilitation, despite significant improvements on the wheelchair circuit and in work capacity. The only significant difference between the groups was found in mechanical efficiency.Implications for rehabilitationThe lack of time-dependent changes in mechanical efficiency and propulsion technique in the group with a recent spinal cord injury, combined with the lack of differences in technique, work capacity and on the wheelchair circuit between the groups, suggest that important adaptations of motor learning may happen even earlier in rehabilitation and emphasize that the group in active rehabilitation was relatively skilled.Standardized observational analyses of handrim wheelchair propulsion abilities during early spinal cord injury rehabilitation provide detailed understanding of wheelchair technique, skill as well as wheelchair propulsion capacity.Measurement of external power output is critical to interpretation of gross efficiency, propulsion technique, and capacity.Wheelchair quality and body weight - next to wheelchair fitness and skill - require careful consideration both in early rehabilitation as well as in the chronic phase of spinal cord injury.


The m(6)A Methyltransferase METTL3 Promotes Translation in Human Cancer Cells.
METTL3 is an RNA methyltransferase implicated in mRNA biogenesis, decay, and translation control through N(6)-methyladenosine (m(6)A) modification. Here we find that METTL3 promotes translation of certain mRNAs including epidermal growth factor receptor (EGFR) and the Hippo pathway effector TAZ in human cancer cells. In contrast to current models that invoke m(6)A reader proteins downstream of nuclear METTL3, we find METTL3 associates with ribosomes and promotes translation in the cytoplasm. METTL3 depletion inhibits translation, and both wild-type and catalytically inactive METTL3 promote translation when tethered to a reporter mRNA. Mechanistically, METTL3 enhances mRNA translation through an interaction with the translation initiation machinery. METTL3 expression is elevated in lung adenocarcinoma and using both loss- and gain-of-function studies, we find that METTL3 promotes growth, survival, and invasion of human lung cancer cells. Our results uncover an important role of METTL3 in promoting translation of oncogenes in human lung cancer.


Colonisation of Clostridium in the body is restricted to hypoxic and necrotic areas of tumours.
The use of gene therapy is one of the most recent molecular strategies for the treatment of cancer. It is essential, however, to have an efficient transfer system by which the desired gene can be delivered to the correct environment. The experiments described in this report investigate apathogenic Clostridium as a possible vector to transfer a specific gene product into the extracellular microenvironment of the tumour which is hypoxic/necrotic in parts, using WAG/Rij rats with transplantable rhabdomyosarcomas as a model. Our data show that Clostridium, after systemic administration of at least 10(7) spores, specifically colonises the hypoxic/necrotic areas of our tumour model, the most efficient species being C. acetobutylicum (NI-4082) and C. oncolyticum. Although spores were also detected in normal tissues for up to 4 weeks, they did not germinate in these tissues. We conclude that it seems likely that these bacteria can be used as a selective transfer system into the extracellular environment of tumours which have hypoxic regions. This strategy would be more tumour-specific than various other strategies that are currently being investigated in anti-cancer gene therapy.


Forgetting induced by recognition of visual images.
Retrieval-induced forgetting is a phenomenon in which groups of stimuli are initially learned, but then a subset of those stimuli are subsequently remembered via retrieval practice, causing the forgetting of the other initially learned items. This phenomenon has almost exclusively been studied using linguistic stimuli. The goal of the present study was to determine whether our memory for simultaneously learned visual stimuli was subject to a similar type of memory impairment. Participants were shown real-world objects, then they practiced recognizing a subset of these remembered objects, and finally their memory was tested for all learned objects. We found that practicing recognition of a subset of items resulted in forgetting of other objects in the group. However, impaired recognition did not spread to new objects belonging to the same category. Our findings have important implications for how our memories operate in real-world tasks, where remembering one object or aspect of a visual scene can cause us to forget other information encoded at the same time.


Mortality After Total Knee and Total Hip Arthroplasty in a Large Integrated Health Care System.
The number of excess deaths associated with elective total joint arthroplasty in the US is not well understood. To evaluate one-year postoperative mortality among patients with elective primary and revision arthroplasty procedures of the hip and knee. A retrospective analysis was conducted of hip and knee arthroplasties performed in 2010. Procedure type, procedure volume, patient age and sex, and mortality were obtained from an institutional total joint replacement registry. An integrated health care system population was the sampling frame for the study subjects and was the reference group for the study. Standardized 1-year mortality ratios (SMRs) and 95% confidence intervals (CIs) were calculated. A total of 10,163 primary total knee arthroplasties (TKAs), 4963 primary total hip arthroplasties (THAs), 606 revision TKAs, and 496 revision THAs were evaluated. Patients undergoing primary THA (SMR = 0.6, 95% CI = 0.4-0.7) and TKA (SMR = 0.4, 95% CI = 0.3-0.5) had lower odds of mortality than expected. Patients with revision TKA had higher-than-expected mortality odds (SMR = 1.8, 95% CI = 1.1-2.5), whereas patients with revision THA (SMR = 0.9, 95% CI = 0.4-1.5) did not have higher-than-expected odds of mortality. Understanding excess mortality after joint surgery allows clinicians to evaluate current practices and to determine whether certain groups are at higher-than-expected mortality risk after surgery.


A biochemical basis for obligate methylotrophy: properties of a mutant of Pseudomonas AM1 lacking 2-oxoglutarate dehydrogenase.
Pseudomonas AMI is a facultative methylotroph which grows on a wide range of carbon compounds. A mutant of Pseudomonas AMI (ICT4I) grew only on C1 compounds and is thus an artificial obligate methylotroph. Measurements of activities of the components of the 2-oxoglutarate dehydrogenase complex suggest that the E2 component (dihydrolipoamide transsuccinylase) is not functional. All other tricarboxylic acid cycle enzymes were present with activities comparable to those in wild-type Pseudomonas AMI and cytochrome levels were unchanged in the mutant. Suspensions of the mutant oxidized pyruvate, lactate, beta-hydroxybutyrate, acetoacetate and 2-oxoglutarate at very low rates. By contrast, C1 compounds were oxidized at the same rate as in wild-type bacteria. Two revertants of ICT4I which regained 2-oxyoglutarate dehydrogenase activity also regained the ability to oxidize and grow on the same substrates as wild-type bacteria. It is concluded that lack of 2-oxoglutarate dehydrogenase may well be the basis of obligate methylotrophy in some bacteria.


Early palliative care in advanced lung cancer: a qualitative study.
BACKGROUND Early ambulatory palliative care (PC) is an emerging practice, and its key elements have not been defined. We conducted a qualitative analysis of data from a randomized controlled trial that demonstrated improved quality of life, mood, and survival in patients with newly diagnosed metastatic non-small cell lung cancer who received early PC integrated with standard oncologic care vs standard oncologic care alone. Our objectives were to (1) identify key elements of early PC clinic visits, (2) explore the timing of key elements, and (3) compare the content of PC and oncologic visit notes at the critical time points of clinical deterioration and radiographic disease progression. METHODS We randomly selected 20 patients who received early PC and survived within 4 periods: less than 3 months (n = 5), 3 to 6 months (n = 5), 6 to 12 months (n = 5), and 12 to 24 months (n = 5). We performed content analysis on PC and oncologic visit notes from the electronic health records of these patients. RESULTS Addressing symptoms and coping were the most prevalent components of the PC clinic visits. Initial visits focused on building relationships and rapport with patients and their families and on illness understanding, including prognostic awareness. Discussions about resuscitation preferences and hospice predominantly occurred during later visits. Comparing PC and oncologic care visits around critical time points, both included discussions about symptoms and illness status; however, PC visits emphasized psychosocial elements, such as coping, whereas oncologic care visits focused on cancer treatment and management of medical complications. CONCLUSIONS Early PC clinic visits emphasize managing symptoms, strengthening coping, and cultivating illness understanding and prognostic awareness in a responsive and time-sensitive model. During critical clinical time points, PC and oncologic care visits have distinct features that suggest a key role for PC involvement and enable oncologists to focus on cancer treatment and managing medical complications.


Gait cycle analysis: parameters sensitive for functional evaluation of peripheral nerve recovery in rat hind limbs.
Video-assisted gait kinetics analysis has been a sensitive method to assess rat sciatic nerve function after injury and repair. However, in conduit repair of sciatic nerve defects, previously reported kinematic measurements failed to be a sensitive indicator because of the inferior recovery and inevitable joint contracture. This study aimed to explore the role of physiotherapy in mitigating joint contracture and to seek motion analysis indices that can sensitively reflect motor function. Data were collected from 26 rats that underwent sciatic nerve transection and conduit repair. Regular postoperative physiotherapy was applied. Parameters regarding step length, phase duration, and ankle angle were acquired and analyzed from video recording of gait kinetics preoperatively and at regular postoperative intervals. Stride length ratio (step length of uninjured foot/step length of injured foot), percent swing of the normal paw (percentage of the total stride duration when the uninjured paw is in the air), propulsion angle (toe-off angle subtracted by midstance angle), and clearance angle (ankle angle change from toe off to midswing) decreased postoperatively comparing with baseline values. The gradual recovery of these measurements had a strong correlation with the post-nerve repair time course. Ankle joint contracture persisted despite rigorous physiotherapy. Parameters acquired from a 2-dimensional motion analysis system, that is, stride length ratio, percent swing of the normal paw, propulsion angle, and clearance angle, could sensitively reflect nerve function impairment and recovery in the rat sciatic nerve conduit repair model despite the existence of joint contractures.


Incomplete flagellar structures in nonflagellate mutants of Salmonella typhimurium.
Incomplete flagellar structures were detected in osmotically shocked cells or membrane-associated fraction of many nonflagellate mutants of Salmonella typhimurium by electron microscopy. The predominant types of these structures in the mutants were cistron specific. The incomplete basal bodies were detected in flaFI, flaFIV, flaFVIII, and flaFIX mutants, the structure homologous to a basal body in flaFV mutants, the polyhook-basal body complex in flaR mutants, and the hook-basal body complex in flaL and flaU mutants. No structures homologous to flagellar bases or their parts were detected in the early-fla group nonflagellate mutants of flaAI, flaAII, flaAIII, flaB, flaC, flaD, flaE, flaFII, flaFIII, flaFVI, flaFVII, flaFX, flaK, and flaM. From these observations, a process of flagellar morphogenesis was postulated. The functions of the early-fla group are essential to the formation of S ring-M ring-rod complexes bound to the membrane. The completion of basal bodies requires succeeding functions of flaFI, flaFIV, flaFVIII, and flaFIX. Next, the formation of hooks attached to basal bodies proceeds by the function of flaFV and by flaR, which controls the hook length. Flagellar filaments appear at the tips of hooks because of the functions of flaL, flaU, and flagellin genes.


Quadricuspid aortic valves in Syrian hamsters and their formation according to current knowledge on valvulogenesis.
Occurrence of quadricuspid aortic valves has been reported in humans, in nine dogs and in a greater white-toothed shrew. Moreover, two cases of developing aortic valves with four anticipated leaflets have been described in Syrian hamster embryos. Currently, however, no case of quadricuspid aortic valve in adult hamsters has been recorded. The aim here is to present four adults of this rodent species, two of them with unequivocally quadricuspid aortic valves and the other two with quadricuspid-like aortic valves. The four anomalous aortic valves were detected among 4,190 Syrian hamsters examined in our laboratory, representing an incidence of 0.09%. None of the affected hamsters showed apparent signs of disease. The present findings are considered on the light of current empirical knowledge about the morphogenesis of quadricuspid and bicuspid aortic and pulmonary valves. Quadricuspid aortic valves result from the partition of one of the normal mesenchymal cushions which normally give rise to normal (tricuspid) valves, while quadricuspid-like valves might be the product of a combined mechanism of fusion and partition of the cushions at the onset of the valvulogenesis. The presence of aortic valves with four leaflets in ancient mammalian lineages such as insectivors and rodents suggest that quadricuspid aortic valves, although showing almost certainly a low incidence, may be widespread among the different groups of mammals, including domestic animals.


Fear of childbirth and sleep quality among pregnant women: a generalized additive model and moderated mediation analysis.
This study aims to examine the associations among fear of childbirth, psychological distress, resilience, and sleep quality among Chinese pregnant women. A cross-sectional survey was carried out between January 2022 to March 2022 among pregnant women who met the inclusion criteria and sought healthcare services at The First Affiliated Hospital of Guangzhou University of Chinese Medicine in Guangdong Province, Southern China. Data was collected using a structured questionnaire that included sociodemographic characteristics, childbirth attitudes questionnaires (CAQ), hospital anxiety and depression scale (HADS), Connor-Davidson resilience scale (CD-RISC), and Pittsburgh sleep quality index (PSQI). A generalized additive model and moderated mediation analysis were employed for data analysis. A non-linear and negative association between fear of childbirth and sleep quality was found in the second trimester and antenatal period. Psychological distress significantly mediated the relationship between fear of childbirth and sleep quality (first trimester: β = 0.044, 95%CI:0.022-0.071; second trimester: β = 0.029, 95%CI:0.009-0.056; third trimester: β = 0.064, 95%CI:0.046-0.088; antenatal period: β = 0.050, 95%CI:0.037-0.063). The moderating role of resilience between fear of childbirth and sleep quality was significant (second trimester: β=-0.006, 95%CI:-0.012-0.001, P = 0.025; antenatal period: β=-0.004, 95%CI:-0.007--0.001, P = 0.014), as well as between fear of childbirth and psychological distress (first trimester: β=-0.016, 95%CI:-0.026--0.005, P = 0.004; antenatal period: β=-0.005, 95%CI:-0.009--0.001, P = 0.014). Fear of childbirth, psychological distress, and resilience are three important factors affecting sleep quality in Chinese pregnant women.


Cytomegalovirus infection and bronchopulmonary dysplasia in premature infants.
During a five-year period, 32 preterm infants weighing less than 2000 g were diagnosed as having postnatally acquired cytomegalovirus (CMV) infection in a neonatal intensive care unit. These CMV-infected infants were matched with 32 uninfected controls for gestational age, birth weight, and birth date; the two groups did not differ in Apgar scores or the incidence of respiratory distress syndrome and patent ductus arteriosus. Roentgenographic evidence of bronchopulmonary dysplasia (BPD) developed in 24 (75%) of 32 CMV-infected infants, an incidence significantly greater than that observed in control infants (12/32; 38%). Infants with acquired CMV infection required more respiratory support and longer hospitalization than uninfected controls. This association between acquired CMV infection in premature infants and the development of chronic lung disease provides further evidence that vigorous efforts to prevent CMV infection in hospitalized neonates is warranted.


Genomic structure, promoter analysis and expression of the porcine (Sus scrofa) TLR4 gene.
Toll-like receptor 4 (TLR4) is essential for initiating the innate response to lipopolysaccharide (LPS) from Gram-negative bacteria by acting as a signal-transducing receptor. As the pig industry faces a unique array of related pathogens, it is anticipated that the genotype of swine TLR4 could be of crucial importance in future strategies aimed at improving genetic resistance to infectious diseases. In order to help in investigating TLR4 as a candidate disease-resistance gene in pigs, we established its genomic structure and produced sufficient flanking intronic sequences to enable simple PCR amplification of the coding portions of the gene. Expression in different porcine tissues was studied and showed splicing variations in mRNA sequences. The cDNA sequence for poTLR4 contains an open reading frame of 2526bp that codes for 841 aa, 98 and 568bp in the 5'- and 3'-UTRs, respectively. Overall, the general organization of porcine, human, murine, and avian TLR4 genes is quite similar: three exons with the third one very long. A high level of conservation of the size and the sequence, especially for the two last exons and particularly in the sequence corresponding to the LRRs and TIR domain, is observed between species. The important antimicrobial properties of these proteins may account for a conservative selection pressure on these TLR4 coding sequences. Several putative binding sites described in the human and murine promoter of TLR4 genes have been identified in the 5'-flanking region of poTLR4. Conversely, this region lacks a TATA box, consensus initiator sequences, or GC-rich regions. The basic sequence data gathered will allow the establishment of an inventory of naturally occurring variation in porcine TLR4, so that alleles can be tested for disease association studies.